Diarrhea kills more than half a million children each year and is the third largest contributor to lost disability adjusted life years. While rehydration addresses the acute consequences of diarrhea, there are no interventions for diarrhea convalescence during which children are at high risk of malnutrition, lower-respiratory tract infections, and recurring diarrhea episodes. Safe and effective interventions to address the long-term consequences of diarrheal disease are urgently needed. Lactoferrin and lysozyme are milk-derived nutritional supplements that may reduce the duration of diarrheal episodes, treat or prevent underlying enteric infections, improve enteric function, and accelerate nutritional recovery. However, it remains unclear whether their antimicrobial action will translate into significant improvements in the long-term clinical and nutritional outcomes of childhood diarrhea. We propose a factorial, double-blind, placebo-controlled, randomized trial to determine the efficacy and mechanisms of lactoferrin and lysozyme supplementation in minimizing the incidence of diarrhea and promoting nutritional recovery among children recovering from diarrhea and wasting. Kenyan children aged 6-24 months who have been discharged from an inpatient or outpatient hospital stay for diarrhea, and have a mid-upper arm circumference [MUAC] <12.5 cm will be randomized to 16-weeks of lactoferrin, lysozyme, a combination of the two, or placebo. This trial will provide much efficacy, mechanistic, and feasibility data from populations most likely to benefit from these interventions.
To improve the long-term consequences of diarrhea, including malnutrition, recurrent diarrhea, and enteric dysfunction, it is critical to identify new, non-antibiotic interventions to reduce underlying intestinal damage and enteric pathogen carriage. This placebo-controlled, four-armed randomized control trial aims to determine the efficacy and mechanisms of action of two safe and inexpensive milk-derived nutritional supplements, lactoferrin and lysozyme, administered for 16-weeks to Kenyan children recovering from medically attended diarrhea and wasting.
